Analyses of radioimmunoassay curves generally depend on the mass action law equations for simple equilibria between a single antigen and antibody. However, most natural protein antigens have multiple different antigenic determinants, and the antisera made to them are multispecific. The behavior of these systems is too complex to solve in a general analytic formulation, so that only individual cases can be treated numerically by computer. We have now developed a general theory for radioimmunoassay binding curves of multideterminant antigens, using probability theory. The only assumptions are that the determinants be unique and independent in their binding to antibodies. The predictive ability of the theory has been demonstrated for antibodies to subregions of the N-terminal third of the beta chain of sickle hemoglobin, studied using antisera fractionated on affinity chromatographic columns of synthetic peptides. One implication is that to obtain quantitative binding parameters, such as affinity constants for multideterminant antigens, one should fractionate the sera to obtain monospecific antibodies.